1. Field of Invention
This invention relates to a process for the preparation of 19-norandrostenedione and key intermediates used in said process. 19-norandrostenedione is a 19-nor steroid having the formula I and is shown in the formulae page.
2. Prior Art
Numerous methods of synthesizing 19-nor steroids have appeared in both the steroid literature and patents over the last 20 years.
The use of the Grignard reagent of 5-bromopentan-2-one propylene ketal as the source of five of the six carbons in the A ring of a steroid is described by L. Velluz, et al., Angew. Chem. Internat. Edit., 4, 181 (1965). Other examples of the use of this Grignard reagent and some of the other reaction steps utilized in the process of the invention are described by M. E. Jung, Tetrahedron, 32, 3 (1976). The Grignard reagent is also mentioned in U.S. Pat. No. 3,413,314.
The preparation of ketone via a Grignard reaction on a mixed anhydride has been described by Mukaiyama et al., Chem. Lett. 663, 687 (1974) and Terasawa et al., Tetrahedron, 33, 595 (1977).
Some of the 19-nor steroids of formulae II and III, shown in Formulae page, are known in the art and are used in the process of this invention.
Wherein A is an alkylidene of 2 to 6-carbon atoms or o-phenylene.
Compound III wherein A is ethylene is disclosed in U.S. Pat. No. 3,646,151. Both compounds III and II wherein A is ethylene are described in German Offen. No. 2,449,031 (August, 1976). Compound IIIa is generically disclosed and compound II is generically suggested in U.S. Pat. No. 4,024,166.
The process of preparing 19-norandrostenedione from compound III is disclosed in U.S. Pat. No. 4,024,166. Compounds III and IV wherein A is ethylene are described in U.S. Pat. No. 4,158,012.